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An elevated IFN\u03b1 signature has been associated with clinically observed neuro-behavioural deficits such as mild cognitive impairment, fatigue, depression and psychosis in these diseases. However, the mechanisms underlying these neuropsychiatric symptoms remain largely unknown, and it is as yet unclear how IFN\u03b1 signalling might influence central nervous system (CNS) function. Aberrant microglia-mediated synaptic pruning and function has recently been implicated in several neurodegenerative and neuropsychiatric diseases, but whether and how IFN\u03b1 modulates these functions are not well defined.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Using a model of peripheral IFN\u03b1 administration, we investigated gene expression changes due to IFNAR signalling in microglia. Bulk RNA sequencing on sorted microglia from wild type and microglia-specific <jats:italic>Ifnar1<\/jats:italic> conditional knockout mice was performed to evaluate IFN\u03b1 and IFNAR signalling-dependent changes in gene expression. Furthermore, the effects of IFN\u03b1 on microglia morphology and synapse engulfment were assessed, via immunohistochemistry and flow cytometry.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that IFN\u03b1 exposure through the periphery induces a unique gene signature in microglia that includes the expected upregulation of multiple interferon-stimulated genes (ISGs), as well as the complement component <jats:italic>C4b<\/jats:italic>. We additionally characterized several IFN\u03b1-dependent changes in microglial phenotype, including expression of CD45 and CD68, cellular morphology and presynaptic engulfment, that reveal subtle brain region-specific differences. Finally, by specifically knocking down expression of IFNAR1 on microglia, we show that these changes are largely attributable to direct IFNAR signalling on microglia and not from indirect signalling effects through other CNS parenchymal cell types which are capable of IFN\u03b1-IFNAR signal transduction.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Peripheral IFN\u03b1 induces unique genetic and phenotypic changes in microglia that are largely dependent on direct signalling through microglial IFNAR. The IFN\u03b1-induced upregulation of <jats:italic>C4b<\/jats:italic> could play important roles in the context of aberrant synaptic pruning in neuropsychiatric disease.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-020-02003-z","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T09:05:56Z","timestamp":1605171956000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Microglial responses to peripheral type 1 interferon"],"prefix":"10.1186","volume":"17","author":[{"given":"Ernest","family":"Aw","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3213-4295","authenticated-orcid":false,"given":"Michael","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,12]]},"reference":[{"key":"2003_CR1","doi-asserted-by":"publisher","first-page":"5459","DOI":"10.4049\/jimmunol.1002795","volume":"192","author":"MK Crow","year":"2014","unstructured":"Crow MK, Type I. 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